Research & Scholarship

Current Research and Scholarly Interests

Infertility

Assisted Reproductive Technologies

Microsurgery and Endoscopic Surgery

Clinical Trials

Day of Embryo Transfer for Patients Undergoing In Vitro FertilizationNot Recruiting

We are examining whether pregnancy rates differ based on day of embryo transfer in patients
who replace all available embryos after an In vitro Fertilization (IVF) cycle. Patients must
be undergoing IVF treatment at Stanford University and patients will not receive compensation
for their participation (no medical costs covered or patient payment for participation).

Stanford is currently not accepting patients for this trial.For more information, please contact Lora Shahine, (650) 498 - 7911.

Abstract

To study pregnancy outcomes between South Asian and Caucasian women undergoing frozen blastocyst transfer cycles.Retrospective cohort study.Not applicable.Caucasian and South Asian patients undergoing frozen blastocyst transfer between January 2011 and December 2014.Not applicable.Live birth rate.A total of 196 Caucasian and 117 South Asian women were included in our study. Indians were on average 2.2 years younger than Caucasian women (34.9 vs. 37.1 years), and were more likely to be nulliparous (59% vs. 43%). All other baseline characteristics were similar. In women undergoing their first frozen ET cycle, implantation rate (49% vs. 47%), clinical pregnancy rate (PR; 54% vs. 49%), and live birth rate (43% vs. 43%) were similar between South Asians and Caucasians, respectively. In patients who underwent a prior fresh blastocyst transfer, the live birth rate was significantly lower in South Asian versus Caucasian women (21% vs. 37%).Our data demonstrate that IVF outcomes are better in frozen versus fresh cycles among South Asian women. The IVF clinics may wish to consider these findings when counseling South Asian patients about the timing of ET.

Abstract

Hyperandrogenic conditions in women are associated with increased rates of miscarriage. However, the specific role of maternal testosterone in early pregnancy and its association with pregnancy outcome is unknown. The purpose of this study was to compare serum testosterone levels during early pregnancy in women with and without polycystic ovary syndrome (PCOS) who either had successful pregnancies or miscarried.We collected serum samples from women attending a university-based fertility centre at the time of their first positive serum beta human chorionic gonadotropin pregnancy test. The samples were subsequently assayed for total testosterone level. We used logistical regression modelling to control for PCOS diagnosis, BMI, and age.Total testosterone levels were available for 346 pregnancies, including 286 successful pregnancies and 78 first trimester miscarriages. We found no difference in total testosterone levels between women who subsequently had an ongoing pregnancy (mean concentration 3.6 ± 2.6 nmol/L) and women with a miscarriage (mean 3.6 ± 2.4 nmol/L). Using the Rotterdam criteria to identify women with PCOS, we also found no differences in serum testosterone between women who had ongoing pregnancies or miscarriages, either with PCOS (P = 0.176) or without PCOS (P = 0.561).Our findings show that early pregnancy testosterone levels do not predict pregnancy outcome, and they call into question the role of testosterone in causing miscarriage in populations of women with PCOS. Further research is needed to elucidate the normal progression of testosterone levels during pregnancy and to investigate further the relationship between PCOS and miscarriage.

Abstract

An estimated 7 million American couples per year seek infertility care in the United States. A male factor contributes to 50% of cases but it is unclear what proportion of infertile couples undergoes male evaluation.We analyzed data from cycles 5 to 7 of the National Survey of Family Growth performed by the Centers for Disease Control to determine the frequency of a male infertility evaluation, and associated reproductive and demographic factors.A total of 25,846 women and 11,067 men were surveyed. Male evaluation was not completed in 18% of couples when the male partner was asked vs 27% when female partners were asked. This corresponds to approximately 370,000 to 860,000 men in the population who were not evaluated at the time of infertility evaluation. Longer infertility duration and white race were associated with increased odds of male infertility evaluation. The male and female samples showed no change in the receipt of male examination with time.Many men from infertile couples do not undergo male evaluation in the United States. Given the potential implications to reproductive goals and male health, further examination of this pattern is warranted.

Abstract

Preimplantation genetic diagnosis (PGD) is an increasingly common adjunct to IVF. The information gained from PGD may be used to reduce the incidence of chromosomally abnormal pregnancies and augment the current selection process of embryos. As such, patients may choose to utilize PGD in either fresh or cryopreserved IVF cycles. It is a common practice to cryopreserve excess embryos at the blastocyst stage. In these cases, trophectoderm biopsy is the only technique available for PGD. This articles reports this study centre's experience with trophectoderm biopsies of cryopreserved blastocysts in 12 patients who underwent 13 cycles of PGD. The implantation rate per embryo transferred was 46% and the ongoing pregnancy rate per embryo transfer was 63%. The results from this case series demonstrate that trophectoderm biopsy on cryopreserved blastocysts to perform PGD is logistically feasible. In addition, the rate of implantation and ongoing pregnancy were maintained within a reasonable range to justify the procedure. Preimplantation genetic diagnosis (PGD) is an increasingly common adjunct to IVF and is used to evaluate the genetic makeup of the embryo prior to transfer of the embryo into the uterus. The information gained from PGD may be used to identify single-gene disorders that result in genetic disease, reduce the incidence of chromosomally abnormal pregnancies and/or augment the selection process of embryos to be transferred. In order to perform PGD, a biopsy of the embryo is the performed and cells are removed for testing. PGD may be performed in either fresh or frozen (cryopreserved) IVF cycles. Patients who have cryopreserved embryos remaining in storage from a previous fresh cycle may wish to have these embryos tested with PGD. Many embryos are frozen on day 5 of development, referred to as the blastocyst stage. At this stage of development, embryo biopsy is performed via a technique known as 'trophectoderm biopsy', in which 1-3 of the cells destined to become the placenta are removed from the embryo for chromosomal testing. We report our experience with trophectoderm biopsy of frozen blastocysts in 12 patients who underwent 13 cycles of PGD. The implantation rate per embryo transferred was 46% and the ongoing pregnancy rate per embryo transfer was 63%. The results from this case series demonstrate that trophectoderm biopsy on cryopreserved blastocysts to perform PGD is logistically feasible. In addition, the rate of implantation and ongoing pregnancy were maintained within a reasonable range to justify the procedure.

Abstract

Untreated hydrosalpinx is known to decrease in vitro fertilization success. We report on 4 patients with hydrosalpinx for whom fresh transfers of 11 good quality embryos did not produce a pregnancy; however, frozen blastocyst transfers in natural cycles resulted in several successful pregnancies, with an implantation rate of 60% (9/15 blastocysts implanted).

Abstract

To examine early pregnancy (EP) testosterone (T) after ovarian stimulation and its effect on singleton pregnancy outcomes.Prospective cohort study.University-based tertiary care center.Subfertile women who conceived with or without fertility treatment.Ovarian stimulation for assisted reproduction, collection of serum total T levels in early pregnancy, and pregnancy follow-up.Rate of preterm delivery, low birth weight (LBW) (<2,500 g), and hypertensive disorders of pregnancy.EP serum samples were measured from 266 singleton pregnancies. The mean T level among spontaneous conceptions was 74.90 ng/dL (SD 48.35 ng/dL); 103 ng/mL was the 90th percentile. Mean EP T was increased among patients who underwent ovarian stimulation compared with nonstimulated control subjects. In patients undergoing IVF, T levels in EP were linearly correlated with the number of oocytes retrieved. When pregnancy outcomes in women with normal T were compared with women with elevated T (>90th percentile), we did not see an increased risk for preterm delivery, hypertensive disorders of pregnancy, LBW infants, or cesarean delivery (odds ratio ratios 1.43, 0.38, 1.39, and 0.85, respectively).Elevations in EP T are associated with ovarian stimulation but do not appear to be associated with adverse pregnancy outcome. Further investigation to determine the etiology of increased maternal and neonatal morbidity among subfertile women is warranted.

Abstract

To investigate the relationship between air bubble position after blastocyst transfer (BT) and pregnancy rates (PRs).Retrospective cohort study.University-based infertility center.Three hundred fifteen consecutive nondonor BTs by a single provider.Catheters were loaded with 25 ?L of culture media, 20 ?L of air, 25 ?L of media containing the blastocysts, 20 ?L of air, and a small amount of additional media. The distance from the air bubble to the fundus, as seen on abdominal ultrasound examination, was measured at the time of transfer. Air bubble location was categorized as <10 mm, 10-20 mm, and >20 mm from the fundus.Clinical pregnancy rate.After controlling for age, parity, FSH and frozen transfers, and accounting for repeated cycles per patient, the PRs for both the >20-mm (38.3%) and the 10-20-mm (42.0%) from the fundus group were significantly reduced compared with the group in which the bubble was <10 mm from the fundus (62.5%).This study is the first to suggest that BT closer to the fundus is associated with higher PR. Although no ectopic pregnancies occurred in the <10-mm group, this outcome should be monitored closely in larger studies.

Abstract

To examine the rate of aneuploidy in missed abortions in patients who conceived after FSH ovarian stimulation compared with women who conceived in a natural cycle.Retrospective cohort.Academic reproductive endocrinology and infertility center.Women with karyotyping of products of conception (POC) from a missed abortion from January 1999 through August 2007. The rate of aneuploidy was compared between patients with a history of infertility who conceived naturally and patients with a history of infertility who conceived with FSH treatment.Ovarian stimulation with FSH, intrauterine insemination, and in vitro fertilization; genetic testing of POC after dilation and curettage.Embryonic karyotype.A total of 229 pregnancies met inclusion criteria, and of these, 64% had an abnormal karyotype. The rate of aneuploidy was 63% in the study group and 70% in the control group. This difference was not statistically significant.The incidence of embryonic aneuploidy was not higher in pregnancies conceived with FSH stimulation compared with spontaneous conceptions in infertility patients. This suggests that exogenous FSH exposure does not increase the risk of aneuploidy.

Abstract

Background. Although the optimal outcome of assisted reproductive technology (ART) is a healthy singleton pregnancy, the rate of twin gestation from ART in women over the age of 35 is persistently high. Methods/Findings. We compared clinical pregnancy rates (PRs), ongoing pregnancy/live birth rates, and multiple gestation rates (MGRs) in 108 women who chose elective single blastocyst transfer (eSBT) to 415 women who chose elective double blastocyst transfer (eDBT) at a hospital-based IVF center. There was no significant difference in PR between eSBT and eDBT (57.4% versus 50.2%, P = 0.47) nor between eSBT and eDBT within each age group: <35, 35-37, 38-40, and >40. The risk of multiple gestations, however, was greatly increased between eSBT and eDBT (1.6 versus 32.4%, P < 0.00005), and this difference did not vary across age groups. Conclusion(s). Women undergoing eDBT are at uniformly high risk of multiple gestation regardless of age. eSBT appears to significantly lower the risk of multiple gestation without compromising PR.

Abstract

Day 2 embryo transfer has been suggested as a method to improve pregnancy rates in poor responders compared with day 3 transfer. Our prospective randomized controlled trial does not show a difference in outcomes based on day of embryo transfer.

Abstract

To determine the impact of infertility on female sexual function.A case-control study.Academic infertility and gynecology practices.One hundred nineteen women with infertility and 99 healthy female controls without infertility between the ages of 18 and 45 years were included in this study.Anonymous survey and Female Sexual Function Index.Female Sexual Function Index scores, frequency of sexual intercourse and masturbation, and sex-life satisfaction.Twenty-five percent of our control group had Female Sexual Function Index scores that put them at risk for sexual dysfunction (<26.55), whereas 40% of our patients with infertility met this criterion. Compared with the control group, the patients with infertility had significantly lower scores in the desire and arousal domains and lower frequency of intercourse and masturbation. The patients with infertility retrospectively reported a sex-life satisfaction score that was similar to that of the controls before their diagnosis, whereas their current sex-life satisfaction scores were significantly lower than those of the controls.Women with a diagnosis of infertility were found to be at higher risk for sexual dysfunction on the basis of their Female Sexual Function Index scores compared with women without infertility. The interaction of sexual function and infertility is complex and deserves further study.

Abstract

To determine the rate of embryonic chromosomal abnormalities, thrombophilias, and uterine anomalies in women over the age of 35 years with recurrent pregnancy loss (RPL).Retrospective cohort study.Academic reproductive endocrinology and infertility clinic.Women>or=35 years old with >or=3 first trimester miscarriages.None.Age, number of prior losses, cytogenetic testing of the products of conception (POC), uterine cavity evaluation, parental karyotype, TSH, and antiphospholipd antibody (APA) and thrombophilia testing. Aneuploidy in the POC in women with RPL was compared with sporadic miscarriages (or=35 years.Among 43 RPL patients, there were 50 miscarriages in which cytogenetic analysis was performed. In the RPL group, the incidence of chromosomal abnormalities in the POC was 78% (39 out of 50) compared with a 70% incidence (98 out of 140) in the sporadic losses. Thrombophilia results in the RPL patients were normal in 38 patients, four patients had APA syndrome, and one had protein C deficiency. Forty out of 43 had normal uterine cavities. Both TSH and parental karyotypes were normal in all of the patients tested. When the evaluation of RPL included karyotype of the POC, only 18% remained without explanation. However, without fetal cytogenetics, 80% of miscarriages would have been unexplained.In older patients with RPL, fetal chromosomal abnormalities are responsible for the majority of miscarriages. Other causes were present in only 20% of cases.

Abstract

Obesity has been identified as a risk factor for spontaneous miscarriage although the mechanism is unclear. The purpose of this study is to better understand the effect of obesity on early pregnancy success by examining the cytogenetic results of miscarriages in women with normal and elevated body mass index (BMI).We conducted a retrospective case-control study in an academic infertility practice. Medical records of women ages <40 years with first trimester missed abortion (n = 204), who underwent dilatation and curettage between 1999 and 2008, were reviewed for demographics, BMI, diagnosis of polycystic ovary syndrome (PCOS) and karyotype analysis. chi(2) and Student's t-test analysis were used for statistical analysis, with P < 0.05 considered significant.A total of 204 miscarriages were included, from women with a mean age of 34.5 years. The overall rate of aneuploidy was 59%. Women with BMI > or = 25 kg/m(2) had a significant increase in euploid miscarriages compared with women with lower BMI (P = 0.04), despite a similar mean age (34.4 years for both).We found a significant increase in normal embryonic karyotypes in the miscarriages of overweight and obese women (BMI > or = 25). These results suggest that the excess risk of miscarriages in the overweight and obese population is independent of embryonic aneuploidy. Further studies are needed to assess the impact of lifestyle modification, insulin resistance and PCOS on pregnancy outcomes in the overweight and obese population.

Abstract

To estimate the effect of ethnicity on in vitro fertilization (IVF) outcomes after blastocyst transfer.We conducted a review of fresh blastocyst transfer IVF cycles from January 1, 2005, to December 31, 2006. Data collection included demographic information, infertility history, treatment protocol details, and treatment outcomes. Statistics were performed using the Student t test and chi2 test. To establish the independent contribution of Asian ethnicity, a multivariable logistic regression analysis was performed.We reviewed 180 blastocyst transfer cycles among white (62%) and Asian (38%) women. The groups were similar in most baseline characteristics. Asian women, however, had a lower body mass index (22.6 compared with 24.2, P=.02), were more likely to be nulligravid (53% compared with 35%, P=.03), and were more likely to have had at least one prior IVF cycle (37% compared with 20%, P=.02) The groups were similar in treatment characteristics, number of oocytes retrieved, fertilization rate, and number of blastocysts transferred. However, Asian women had a thicker endometrial lining (10.9 compared with 10.2, P=.02). Despite these similarities, Asian women had a lower implantation rate (28% compared with 45%, P=.01), clinical pregnancy rate (43% compared with 59%, P=.03), and live birthrate (31% compared with 48%, P=.02). In multivariable analysis, the decreased live birthrate among Asian women persisted (adjusted odds ratio 0.48, 95% confidence interval 0.24-0.96, P=.04).When compared with white women, Asian women have lower clinical pregnancy and live birthrates after blastocyst transfer.

Abstract

Disease prevalence and response to medical therapy may differ among patients of diverse ethnicities. Poor outcomes with in vitro fertilization (IVF) treatment have been previously shown in Indian women compared to Caucasian women, and some evidence suggests that poor embryo quality may be a cause for the discrepancy. In our center, only patients with the highest quality cleavage stage embryos are considered eligible for extending embryo culture to the blastocyst stage. We compared live birth rates (LBR) between Indian and Caucasian women after blastocyst transfer to investigate whether differences in IVF outcomes between these ethnicities would persist in patients who transferred similar quality embryos.In this retrospective cohort analysis, we compared IVF outcome between 145 Caucasians and 80 Indians who had a blastocyst transfer between January 1, 2005 and June 31, 2007 in our university center. Indians were younger than Caucasians by 2.7 years (34.03 vs. 36.71, P = 0.03), were more likely to have an agonist down regulation protocol (68% vs. 43%, P<0.01), and were more likely to have polycystic ovarian syndrome (PCOS), although not significant, (24% vs. 14%, P = 0.06). Sixty eight percent of Indian patients had the highest quality embryos (4AB blastocyst or better) transferred compared to 71% of the Caucasians (P = 0.2). LBR was significantly lower in the Indians compared to the Caucasians (24% vs. 41%, P<0.01) with an odds ratio of 0.63, (95%CI 0.46-0.86). Controlling for age, stimulation protocol and PCOS showed persistently lower LBR with an adjusted odds ratio of 0.56, (95%CI 0.40-0.79) in the multivariate analysis.Despite younger age and similar embryo quality, Indians had a significantly lower LBR than Caucasians. In this preliminary study, poor prognosis after IVF for Indian ethnicity persisted despite limiting analysis to patients with high quality embryos transferred. Further investigation into explanations for ethnic differences in reproduction is needed.

Abstract

To evaluate the pregnancy rate, ovarian responsiveness, and endometrial thickness in infertility patients with a history of methotrexate exposure who subsequently underwent controlled ovarian stimulation.Retrospective cohort study.University reproductive endocrinology and infertility program.Forty-eight women with infertility undergoing ovarian stimulation after receiving methotrexate treatment for ectopic gestation.Methotrexate administration and controlled ovarian stimulation.Pregnancy rate, cycle day 3 FSH levels, number of oocytes retrieved, and endometrial thickness.The cumulative intrauterine pregnancy rate achieved with controlled ovarian stimulation at 2 years after methotrexate exposure was 43%, with a mean time to conceive of 181 days. Thirty-five patients with similar fertility treatments pre- and post-methotrexate were identified. Within this group, when an IVF cycle occurred within 180 days of methotrexate exposure, a significant decline in oocytes retrieved was observed. Cycles performed later than 180 days after methotrexate exposure did not exhibit a decrease in oocyte production. Endometrial development was similar at all time points examined.These findings suggest a time-limited and reversible impact of methotrexate on oocyte yield. If confirmed by larger clinical series and/or animal data, these results may impact the management of ectopic gestation in the patient with a history of infertility or the timing of subsequent treatments.

Abstract

To evaluate the cost effectiveness of laparoscopy for unexplained infertility.We performed a cost-effectiveness analysis using a computer-generated decision analysis tree. Data used to construct the mathematical model were extracted from the literature or obtained from our practice. We compared outcomes following four treatment strategies: [1] no treatment, [2] standard infertility treatment algorithm (SITA), [3] laparoscopy with expectant management (LSC/EM), and [4] laparoscopy with infertility therapy (LSC/IT). The incremental cost-effectiveness ratio (ICER) was calculated, and one-way sensitivity analyses assessed the impact of varying base-case estimates.Academic in vitro fertilization practice.Computer-simulated patients assigned to one of four treatments.Fertility treatment or laparoscopy.Incremental cost-effectiveness ratios.Using base-case assumptions, LSC/EM was preferred (ICER =$128,400 per live-birth in U.S. dollars). Changing the following did not alter results: rates and costs of multiple gestations, penalty for high-order multiples, infertility treatment costs, and endometriosis prevalence. Outcomes were most affected by patient dropout from infertility treatments-SITA was preferred when dropout was less than 9% per cycle. Less important factors included surgical costs, acceptability of twins, and the effects of untreated endometriosis on fecundity.Laparoscopy is cost effective in the initial management of young women with infertility, particularly when infertility treatment dropout rates exceed 9% per cycle.

Abstract

To investigate the hypothesis that surgical treatment of endometriosis in infertile patients may improve pregnancy rates by improving embryo quality.We conducted a retrospective evaluation of 30 infertile patients treated with in vitro fertilization (IVF) before and after surgery for endometriosis. Patients served as their own controls and only cycles with similar stimulation protocols were compared.Using standard visual evaluation, embryo quality on day 3 was similar before and after surgical treatment of endometriosis. Fifty seven percent of patients had stage I-II endometriosis and 43% had stage III-IV disease. No patients had a live birth after the first IVF cycle and 43% of patients had a live birth with the IVF cycle after surgery.Surgical treatment of endometriosis does not alter embryo quality in patients with infertility treated with IVF.

Abstract

To determine whether an elevated basal FSH concentration is an independent predictor of fetal aneuploidy, as measured in spontaneous abortions (SAB).Retrospective study.Academic reproductive endocrinology and infertility center.All women with karyotypes of chorionic villi isolated from first trimester spontaneous miscarriages at the time of dilation and curettage from 1999 to 2006. The highest basal serum FSH level in the year preceding dilation and curettage was recorded.Monitoring of early pregnancy.Fetal karyotype.A total of 177 spontaneous miscarriages with karyotypes (70 euploid and 107 aneuploid) were identified, of which 53% were conceived by IVF. The aneuploid cohort consisted of trisomic (87%), teraploid (9.3%), and monosomic (3.7%) gestations. Using logistic regression analysis, basal FSH was not found to be independently predictive of an aneuploid gestation in our data set.Our data do not support the hypothesis that an elevated basal FSH concentration is associated with an increase in fetal aneuploidy. Our findings suggest that the association between diminished ovarian reserve and SAB may result from nonkaryotypic factors.

Two cases of cholestasis in the first trimester of pregnancy after ovarian hyperstimulationFERTILITY AND STERILITYZamah, A. M., El-Sayed, Y. Y., Milki, A. A.2008; 90 (4)

Abstract

To report two cases of early onset cholestasis of pregnancy associated with IVF and ovarian hyperstimulation syndrome.Case report.University-based IVF program.Two patients with first-trimester cholestasis of pregnancy after IVF that was associated with ovarian hyperstimulation syndrome.In vitro fertilization-embryo transfer, management of hyperstimulation syndrome, and cholestasis of pregnancy.Clinical pregnancy course and pregnancy outcomes.The first patient was treated with ursodeoxycholic acid and had resolution of symptoms within the first trimester. The second patient initially had a miscarriage but did redevelop cholestasis of pregnancy in the latter stages of a pregnancy resulting from frozen embryo transfer.We report two cases of intrahepatic cholestasis of pregnancy in the first trimester of pregnancies by IVF in association with ovarian hyperstimulation syndrome and markedly elevated maternal serum estrogen levels. Early recognition of this unusual clinical presentation allows for optimal pregnancy management by both the reproductive endocrinologist and the obstetrician.

Abstract

Hemorrhage from a cervical pregnancy is a time-sensitive matter. Effective temporization measures for the initial management of this hemorrhage have not previously been reported in the literature.A 43-year-old woman, gravida 0, underwent in vitro fertilization and embryo transfer. She subsequently presented to the office with sudden onset of vaginal hemorrhage due to a cervical pregnancy. Cervical artery sutures were placed, and a cervical vasoconstricting agent was injected, at which point the patient's bleeding stopped. She then underwent successful treatment with dilation and curettage.Conservative measures to manage hemorrhage due to cervical pregnancy can be initiated, with possible rapid establishment of hemostasis until definitive treatment can be achieved.

Abstract

To evaluate the frequency of specific aneuploidies in miscarriages in an infertility practice and calculate the potential sensitivities of the different aneuploidy screening options for preimplantation genetic diagnosis (PGD) in this setting.Retrospective analysis.Academic reproductive endocrinology and infertility practice.Women with miscarriages that had karyotype analysis on products of conception.None.Karyotype of spontaneous abortions compared with commercially available PGD options.Of the 273 karyotypes analyzed, 177 (64.8%) were abnormal. The average age of the patients was 37 +/- 4.5 years. Using a limited five-probe panel, 54 of the 177 (31%) abnormal karyotypes would have been detected. In contrast, an extended PGD panel (using 9, 10, or 12 chromosome probes) would have detected 127, 131, and 140 of 177 abnormalities, 72%, 74%, and 79% respectively. The difference between the limited (5-probe) and extended (9-, 10-, and 12-probe) panels was statistically significant. There was not a statistically significant difference among the extended panels.Most of the abnormalities seen in miscarriages are detectable by PGD with extended panels. A significantly higher percentage of these abnormalities could be detected by screening for 9, 10, or 12 chromosomes compared with only 5.

Abstract

A retrospective review of all patients older than 35 who underwent elective single blastocyst transfer was performed. Twenty-three of the 45 patients (51.1%) have an ongoing pregnancy or liveborn delivery, with a mean age of 37.3 years, demonstrating a clear role for elective single transfer in this relatively older IVF population.

Abstract

The objective of this study is to determine the rate of abnormalities detected by cytogenetic testing of first trimester miscarriages, in patients with and without an embryonic pole seen on ultrasound.A retrospective study of 272 D&Cs for missed abortions in an academic infertility practice from 1999 to 2006. Karyotype results were compared with transvaginal ultrasound findings. Chi-squared analysis was used with a P < 0.05 for significance.There was a high rate of abnormal karyotypes in all miscarriages (65%). Rates of abnormal karyotypes were 58% and 68% in cases with anembryonic gestations and those with a fetal pole seen, respectively (P > 0.05).The high rate of abnormalities detected in both groups suggests that useful results can be obtained from chromosomal testing of the POC regardless of ultrasound findings. Further studies on the prognostic value and cost effectiveness of chromosomal testing are needed.

Abstract

To compare the rate of ectopic pregnancy (EP) with fresh versus frozen blastocyst transfer in our program during the same time period.Retrospective analysis.University IVF program.Women who achieved a clinical pregnancy after IVF between 1998 and 2005.In our program, cryopreservation is performed at the blastocyst stage. Embryo transfer was performed 1 to 1.5 cm short of the fundus by abdominal ultrasound guidance.The incidence of EP was examined in relation to fresh versus frozen blastocyst transfer.In the frozen blastocyst group, there were 5 EPs out of 180 clinical pregnancies (2.8%), and there were 10 EPs out of 564 clinical pregnancies (1.8%) in the fresh blastocyst group.The rate of EP is not significantly increased after the transfer of frozen thawed blastocysts compared with fresh blastocyst transfer.

Abstract

The purpose of our study is to compare the occurrence of monozygotic twinning (MZT) from blastocyst transfer (BT) in our program between an earlier and more recent time period.Retrospective.Academic IVF practice.All pregnancies conceived between March 2002 and December 2005 (N = 932) in our program were compared to pregnancies conceived before March 2002 (N = 554), which were the subject of a previous study.None.The incidence of MZT with day 3 embryo transfer and BT were compared between the study and control groups.During the study period, the rate of MZT was not significantly different for BT at 2.3% (9/385) compared to day 3 embryo transfer at 1.8% (10/547). This rate of 2.3% for BT was significantly lower than the rate of 5.6% (11/197) reported at our institution for BT before March 2002.Our study suggests that the risk of MZT with BT is significantly lower in the more recent time period and is in the range of what is seen with cleavage stage transfer. It is likely that improvements in culture systems as experience is gained with BT played a role.

Abstract

We compared the effects of two standard oxygen concentrations, physiological (5% O(2), 5% CO(2), and 90% N(2)) and atmospheric (5% CO(2) with the balance as air), on fertilization, embryo development, and pregnancy rate in 106 patients undergoing IVF, excluding donor oocyte cycles and preimplantation genetic diagnosis cycles. The differences in oxygen concentration did not significantly affect fertilization rate, blastocyst formation, or pregnancy rate, but there was a significant difference in mean embryo score between physiological and atmospheric groups on day 3.

Abstract

To evaluate the effect of oral contraceptive pill (OCP) pretreatment in patients undergoing IVF cycles with an antagonist.In this retrospective study, 194 cycles of women with diminished ovarian reserve undergoing IVF with a protocol using GnRH antagonists were evaluated. Oral contraceptive pretreatment was used in 146 cycles.Pregnancy rates were the same in both groups. Patients using OCPs required more gonadotropins (5,890 IU) compared to patients not undergoing OCP pretreatment (4,410 IU).Pregnancy outcomes were the same whether or not OCP pretreatment was implemented in poor responders using an antagonist protocol. While OCP pretreatment may help with scheduling flexibility, the higher dose of gonadotropins needed for ovarian stimulation should be considered.

Abstract

Many will agree that the use of laparoscopy to diagnose and potientially treat endometriosis in patients who suffer from infertility has been superseded by IVF and sometimes oocyte donation, especially in older patients. The findings of our study add another dimension to management of endometriosis in the setting of infertility and emphasize the importance of keeping laparoscopy in the infertility management equation.

Abstract

Thromboembolic phenomena are a serious consequence of assisted reproductive technology. We present a case of upper extremity deep vein thrombosis (DVT) at 7 weeks gestation following ovarian hyperstimulation syndrome (OHSS) and IVF. Three weeks after recovering from OHSS, the patient presented with left neck pain and swelling. Ultrasound revealed a thrombus in the left jugular vein and left subclavian vein. Low molecular weight heparin (LMWH) was initiated with symptom resolution within 1 week. The patient remained on LWMH throughout her pregnancy and delivered at term. A literature review showed 97 published cases of thromboembolism following ovulation induction. A majority of these cases was associated with OHSS and pregnancy and the site of involvement was predominantly in the upper extremity and neck. Infertility physicians and obstetricians should be aware of this complication and keep in mind that it may occur weeks after resolution of OHSS symptoms.

Abstract

To report our experience in patients with previous IVF failures who conceived after laparoscopic treatment of endometriosis.Retrospective case series.Tertiary center IVF and endoscopy programs.Infertility patients with history of prior IVF failures.Laparoscopic evaluation and treatment of endometriosis by the same surgeon.Occurrence of conception after laparoscopic treatment of endometriosis.Of 29 patients with prior IVF failures, 22 conceived after laparoscopic treatment of endometriosis, including 15 non-IVF pregnancies and 7 IVF pregnancies.In the absence of tubal occlusion or severe male factor infertility, laparoscopy may still be considered for the treatment of endometriosis even after multiple IVF failures.

Abstract

Small, intramural leiomyomas are not generally considered a risk factor for poor reproductive outcomes.A patient with a 6-mm intramural leiomyoma and a normal uterine cavity by hysteroscopic evaluation who conceived after in vitro fertilization developed severe early-onset intrauterine growth restriction (IUGR), leading to pregnancy termination at 23.4 weeks' gestation. At 6 weeks postpartum, a 1.7-cm, intracavitary leiomyoma was detected on ultrasound evaluation and removed by hysteroscopic resection. The patient conceived in a subsequent in vitro fertilization cycle and gave birth to monozygotic twins with appropriate weights at 34 weeks of gestation. In the absence of other identifiable etiologies of the IUGR, it is plausible that the small, intramural leiomyoma enlarged and migrated into the cavity, causing abnormal placentation and leading to fetal growth restriction in the first pregnancy.Uterine cavity reevaluation is recommended in the investigation of IUGR before a woman attempts further pregnancies.

Abstract

To report on a patient with a monochorionic triamnionic triplet pregnancy after IVF with donor oocytes.Case report.Academic tertiary care hospital.A 42-year-old woman who underwent IVF with donor oocytes.After failed IVF attempts, the patient chose to undergo treatment with donor oocytes. Her 23-year-old oocyte donor underwent standard controlled ovarian hyperstimulation. Retrieved oocytes were fertilized in vitro, and two embryos were transferred at the blastocyst stage.Intrauterine pregnancy with single gestational sac and three fetal poles with cardiac activity.After extensive counseling with perinatologists about pregnancy complications, the patient elected to terminate at 10 weeks of gestation.Several processes have been suggested to explain the increase in monozygotic twinning after IVF. These factors include advanced maternal age, superovulation, manipulation of the zona pellucida, and prolonged culture. It is possible that other factors may also play a role, especially in high-order monozygotic multiple pregnancies. All patients should be informed of the potential risk of a high-order multiple pregnancy after IVF, even when only one or two embryos are transferred.

Abstract

To present a case involving the transfer of a single pronucleated oocyte resulting in a monozygotic twin pregnancy.A descriptive case report of a single patient.The patient conceived and was found to have a monochorionic diamnionic pregnancy which resulted in the birth of normal identical twin boys at 32 weeks of gestation.The case report addresses an issue that has not received proper attention in the literature. It illustrates that observing a single PN in an oocyte at fertilization check should not be an absolute deterrent to transferring the resulting embryo even in an older patient with a high FSH level. This report also suggests that single observations, especially at the assessment of fertilization, in the IVF laboratory are limited when evaluating embryo potential and normalcy.

Abstract

To report successful pregnancies in the setting of exaggerated endometrial thickness.Case report.Two infertility practices.Two IVF patients.IVF and ET.Endometrial thickness on the days of hCG injection, oocyte retrieval, and ET.Two successful twin pregnancies, each after the transfer of two embryos, in the setting of an endometrial thickness of 16 mm in one case and 20 mm in the other.This report illustrates the possibility for a successful outcome in the setting of an exaggerated endometrial thickness, including for the first time a value of 20 mm on the day of egg retrieval.

Abstract

This report describes our initial experience with elective single blastocyst transfer in 19 patients who had a mean age of 36.3 +/- 2.4 years. The ongoing pregnancy rate, 53% after the fresh embryo transfer and 68% when thaw cycles are included, suggests that single blastocyst transfer has a place in this relatively older patient population.

Abstract

In a retrospective analysis of 623 clinical pregnancies conceived after IVF, a 5.4% ectopic pregnancy rate (14/258 clinical pregnancies) was found in cases where assisted hatching (AH) was performed compared to 2.2% (8/365) in the group without assisted hatching. In view of the widespread use of AH, it may be relevant to assess the effect of AH on the incidence of ectopic pregnancy in a large multicenter effort.

Abstract

To reassess the use of TEST-yolk buffer (TYB) in an in vitro fertilization (IVF) program by comparing fertilization rates achieved in a glucose-free cleavage medium by the standard IVF preparation of sperm versus a 2-h, room temperature incubation of sperm in TYB.Oocytes collected for IVF were randomly split into two groups and inseminated with either TYB-treated sperm or IVF-prepared sperm.Stanford Reproductive Endocrinology and Infertility Center.Fifty couples undergoing IVF with at least 10 mature oocytes.Fertilization rates in vitro.Fertilization rates were significantly higher (p = 0.015) with TYB treatment. The average 2PN fertilization rate was 49.6% (188/379) for the IVF group and 57.4% (221/385) in the IVF with TYB group.A 2-h, room temperature incubation of sperm in TYB produces significantly higher 2PN fertilization rates as compared to standard IVF preparation of sperm in a current generation cleavage medium.

Abstract

To evaluate the incidence of aneuploidy in miscarriages after IVF and intracytoplasmic sperm injection (ICSI) procedures.Retrospective study.University IVF program.All IVF patients with missed abortions undergoing uterine curettage.Cytogenetic analysis of products of conception (POC).Incidence of aneuploidy in POC.Thirty-two of 59 specimens (54%) reviewed were abnormal. The patients with ICSI were more likely to have aneuploidy identified in their POC than conventional IVF, 76% vs. 41%. The average ages in these groups were similar: 37.1 vs. 37.8 years. There was a trend toward decreased aneuploidy with day 5 compared to day 3 embryo transfers; 38% vs. 63%.We found a significantly higher aneuploidy rate in the abortuses of patients who conceived with ICSI. It is possible that this increased incidence is due to abnormalities in the sperm of patients with ICSI, but could also be partially related to the technique itself.

Abstract

Hysteroscopy offers diagnostic accuracy and the ability to treat uterine pathology, but practitioners may be reluctant to perform it without a high index of suspicion because it traditionally requires an operating room. This study reviews the findings and feasibility of office-based diagnostic and operative hysteroscopy in an unselected in vitro fertilization (IVF) population to evaluate whether first-line hysteroscopy should be recommended.One thousand consecutive infertile patients scheduled for in vitro fertilization underwent office hysteroscopy. A rigid 20-degree 5-mm hysteroscope, with an operative channel for grasping forceps, scissors, or coaxial bipolar electrode was used. Operative findings, complications, and patient tolerance were noted.Sixty-two percent of patients had a normal uterine cavity. Thirty-two percent had endometrial polyps. Other pathology included submucous fibroids (3%), intrauterine adhesions (3%), polypoid endometrium (0.9%), septum (0.5%) retained products of conception (0.3%), and bicornuate uterus (0.3%). The pathology was treated in all patients without complication.When hysteroscopy is routinely performed prior to in vitro fertilization, a significant percentage of patients have uterine pathology that may impair the success of fertility treatment. Patient tolerance, safety, and the feasibility of simultaneous operative correction make office hysteroscopy an ideal procedure.

Abstract

The purpose of this study was to determine the consistency in the uterine position between mock and real embryo transfer.We reviewed 996 consecutive embryo transfer cycles (585 patients); 74% of patients had an anteverted (AV) uterus and 26% had a retroverted (RV) uterus at mock embryo transfer. All mock and real embryo transfers were performed under abdominal ultrasound guidance.Of 623 fresh embryo transfers in patients with an AV uterus at mock embryo transfer, only 2% became RV, while 55% of 213 embryo transfers in patients with an RV uterus on mock embryo transfer converted to AV at real embryo transfer (P < 0.0001). For frozen-thawed embryo transfer, 12% of AV uteri at mock embryo transfer became RV, while 33% of RV uteri became AV (P = 0.01).Our data suggest that an RV uterus at mock embryo transfer will often change position at real embryo transfer. Misdirecting the embryo transfer catheter can be avoided by accurate knowledge of the uterine position at the time of embryo transfer, which can be more accurately assessed by routine ultrasound guidance. Additionally, patients with an RV uterus at mock embryo transfer should still present with a full bladder for embryo transfer, since a significant number will convert to an AV position.

Abstract

To report the occurrence and management of hydrometra at the time of scheduled embryo transfer in two patients who underwent drainage of hydrosalpinges at oocyte retrieval.Case report. University IVF clinic.Two patients with hydrosalpinges visible on ultrasonography who deferred tubal surgery. Although no fluid was seen at the time of oocyte retrieval, hydrometra was noticed and drained before planned embryo transfer (ET).Reoccurrence of hydrometra after drainage.Rapid reaccumulation of hydrometra despite drainage was seen in both patients, one of whom had reoccurrence in 1 hour. Embryo transfer was deferred until after tubal surgery, and all embryos were cryopreserved.In patients with hydrosalpinges, ultrasonography before ET is useful to detect newly developed hydrometra. Aspiration of the uterine fluid is unlikely to help because of rapid reaccumulation of hydrometra. Cryopreservation of the embryos for future transfer after the hydrosalpinx is removed or ligated is recommended.

Abstract

Uterus didelphys with obstructed hemivagina presents with a pelvic mass often inappropriately approached by laparotomy.An adolescent female was evaluated for dysmenorrhea, a pelvic mass and a double uterus. Transvaginal resection of the oblique vaginal septum was performed, with relief of symptoms and subsequent conception.This entity should be considered to prevent misdiagnosis and unnecessary abdominal surgery.

Abstract

The incidence of ovarian torsion has been reported to be increased during controlled ovarian hyperstimulation. In this report we describe exercise-induced ovarian torsion in an ovary with a persistent cyst, following a failed gonadotrophin-stimulated intra-uterine insemination cycle. This report suggests that the risk of ovarian torsion persists beyond the treatment cycle and that patients should be instructed to refrain from exercise or strenuous activity if regression to normal ovarian size has not been documented. Ovarian torsion should be high in the differential diagnosis in patients experiencing abdominal pain with a history of recent gonadotrophin stimulation.

Abstract

To evaluate the sex ratio in births conceived with blastocyst transfer compared to day 3-ET.A retrospective analysis of IVF patients who became pregnant after blastocyst or cleavage stage transfer at Stanford University Hospital and a literature review were performed.In the day 3-ET group, the male-to-female (M/F) ratio was 157/139 (53%/47%) compared to 97/66 (59.5%/40.5%) in the blastocyst group (P = 0.18). Similar trends have been found in individual studies in the literature but reached statistical significance in only one out of six reports reviewed. The combined data from our study and the literature show a male-to-female ratio of 797/594 (57.3%/42.7%) in blastocyst transfer compared to 977/932 (51.2%/48.8%) in day 3-ET (P = 0.001).Although individual studies may lack power to show an altered sex ratio with blastocyst transfer, the combined data presented in this report do suggest that the M/F ratio is higher with blastocyst transfer compared to cleavage stage transfer.

Abstract

This report describes three cases in which the addition of recombinant HCG to urinary HCG to trigger ovulation in IVF improved oocyte recovery in patients with a history of scant oocyte yield in previous cycles.

Abstract

To describe a case of primary infertility associated with oocytes having one pronucleus before fertilization on repeated IVF attempts.Case report.A university-based assisted reproduction unit.A 30-year-old woman with primary infertility and oocytes containing one pronucleus before fertilization.Oocyte donation.Pregnancy.Conceived triplets after transfer of three embryos using donor oocytes.This patient's infertility was likely associated with an oocyte abnormality, as evidenced by the premature formation of one pronucleus before fertilization. In the future, more studies on the appearance of a single pronucleus before fertilization will be needed to determine its overall significance on fertility.

Abstract

To investigate whether ICSI (intracytoplasmic sperm injection) results in decreased blastocyst formation and pregnancy compared to IVF (in vitro fertilization).We performed a retrospective analysis of blastocyst transfer (BT) offered routinely to patients under age 40 with > or = three 8-cell embryos on day 3 and compared IVF to ICSI cycles. Sequential media were used with P1 until day 3, then Blastocyst Medium until day 5/6.There were 131 IVF and 75 ICSI cycles. There was no difference in age, number of oocytes, zygotes, 8-cell embryos, blastocysts on days 5 and 6, or embryos transferred. Progression to blastocyst was similar (78% for IVF and 73% for ICSI) as was the viable pregnancy rate (51.4% for IVF and 55% for ICSI). No cycles failed to form blastocysts.The progression to blastocyst and the likelihood of conceiving a viable pregnancy were unaltered by ICSI. Thus it seems appropriate for programs to offer BT to patients undergoing ICSI using the same inclusion criteria applied to their IVF patients.

Abstract

To evaluate the incidence of monozygotic twinning (MZT) in pregnancies conceived after blastocyst transfer compared to cleavage-stage transfer.Retrospective study.University IVF program.All IVF patients with viable pregnancies conceived during a 4-year period.Blastocyst transfer or day 3 ET.Incidence of MZT assessed by transvaginal ultrasound.There were 11 incidences of MZT in 197 viable pregnancies (5.6%) with blastocyst transfer compared to 7 of 357 viable pregnancies (2%) with day 3 ET. In 10 of 18 pregnancies, MZT was observed in the setting of a higher order multiple gestation (6 of 11 for blastocyst transfer and 4 of 7 for day 3 ET). In the day 3 ET group, assisted hatching or intracytoplasmic sperm injection (ICSI) did not increase MZT (4 of 213, 1.9%) compared to cycles without zona breaching (3 of 144, 2.1%). Similarly, in the blastocyst-transfer group, ICSI did not increase the incidence of MZT (4 of 74, 5.5% for ICSI and 7 of 123, 5.7% for non-ICSI IVF).Compared to day 3 ET, blastocyst transfer appears to significantly increase the incidence of gestations with MZT. This information should be taken into account when counseling patients about the pros and cons of extended culture.

Effect of hysteroscopy performed in the cycle preceding controlled ovarian hyperstimulation on the outcome of in vitro fertilizationFERTILITY AND STERILITYMooney, S. B., Milki, A. A.2003; 79 (3): 637-638

Abstract

BACKGROUND: Blastocyst transfer may theoretically decrease the incidence of ectopic pregnancy following IVF-ET in view of the decreased uterine contractility reported on day 5. The purpose of our study is to specifically compare the tubal pregnancy rates between day 3 and day 5 transfers. METHODS: A retrospective analysis of all clinical pregnancies conceived in our IVF program since 1998 was performed. The ectopic pregnancy rates were compared for day 3 and day 5 transfers. RESULTS: There were 623 clinical pregnancies resulting from day 3 transfers of which 22 were ectopic (3.5%). In day 5 transfers, there were 13 ectopic pregnancies out of 333 clinical pregnancies (3.9%). The difference between these rates is not statistically significant (P = 0.8). CONCLUSIONS: Our data suggests that the ectopic pregnancy rate is not reduced following blastocyst transfer compared to day 3 transfer. While there may be several benefits to extended culture in IVF, the decision to offer blastocyst transfer should be made independently from the issue of ectopic pregnancy risk.

Abstract

To compare cycle outcomes in similar populations of women over 40 who underwent blastocyst transfer compared with women who had day 3 embryo transfer with assisted hatching (ET/AH).Retrospective study. STTING: University hospital-based program.Eighty-six IVF cycles in women ages 40 to 43 years who had more than three eight-cell embryos on day 3. On day 3 of embryo culture, patients chose either to undergo blastocyst transfer or day 3 ET/AH.Pregnancy and cryopreservation rates were recorded.In 48 cycles, blastocyst transfer was performed, and in 38 cycles day 3 ET/AH was performed. There was no statistically significant difference between the blastocyst transfer group and the day 3 ET/AH group with respect to age (41.1 +/- 0.9 years vs. 41.6 +/- 0.8 years), percentage of intracytoplasmic sperm injection cycles (29.2% vs. and 27.6%), number of oocytes (14.9 +/- 5.6 vs. 12.8 +/- 4.0), or number of eight-cell embryos (6.1 +/- 2.2 vs. 5.4 +/- 1.5). Significantly fewers embryos were transferred per cycle with blastocyst transfer (2.6 +/- 1.0) compared with day 3 ET/AH (5.9 +/- 2.0). The viable pregnancy rate was similar in the blastocyst transfer group (29.2%) and in the day 3 ET/AH group (26.3%). Embryos for cryopreservation were available in significantly more cycles in the blastocyst transfer group (52.1%) than in the day 3 ET/AH group (21.1%). Cleavage stage arrest occurred only in one cycle.Blastocyst transfer appears to be as effective as day 3 ET/AH in older patients with good embryos. Higher cryopreservation rate in the blastocyst transfer group may represent an advantage over day 3 ET/AH. Older women may also benefit from the information that extended culture provides them regarding their oocyte quality.

Abstract

To determine if careful specimen selection and washing of tissue from first trimester missed abortion products of conception specimens increases the sensitivity of routine cytogenetics in detecting aneuploidy.Retrospective review of cytogenetics results from tissue from dilation and curettage for missed abortion in a university fertility practice between 1998 and 2001. A technique of careful selection and washing of the specimen was implemented in July 1999. Results from before (n = 15) and after (n = 41) this change were compared. Cytogenetics reports from other physicians using the same laboratory were used for comparison (n = 59).The percentage of 46XX results was significantly decreased in the test group when compared to historical and community controls: 29% vs. 73% and 56% respectively. The percentage of aneuploid results was significantly higher in the test group at 61% vs. 7% and 36% in the historical and community controls respectively.Thorough separation and cleaning of villi prior to sending missed abortion specimens significantly increases sensitivity of conventional cytogenetics for detecting aneuploidy by decreasing maternal contamination.

Abstract

Endometriosis in Turner's syndrome patients has only been reported in five isolated cases. We present here an endometrioma on the uterine serosa and pelvic endometriosis arising in a mosaic Turner's patient receiving hormone replacement therapy (HRT). The 24 year old patient with mosaic Turner's syndrome [45,X; 46,X pseudo dicentric Y (q11.23)], on cyclic HRT after laparoscopic gonadectomy 5 years previously, was found to have an adnexal mass on routine examination. Given her history, due to the fear of a malignant process arising from a potential gonadal remnant, she underwent a laparoscopy and was found to have a 5 cm serosal endometrioma arising on a stalk from the uterine fundal surface as well as pelvic endometriosis. De-novo endometrioma and endometriosis occurred in a mosaic Turner's patient after gonadectomy on cyclic HRT. The presentation was also unusual with a pedunculated endometrioma arising from the uterine serosa. Due to the fact that the patient did have cyclic menstrual flow, her endometriosis may have arisen from retrograde menstruation or coelomic metaplasia induced by exogenous hormones.

Abstract

Vascular injury is the most urgent type of trauma at laparoscopy. It is thought that the rate of vascular injury may increase as the complexity of laparoscopic surgery increases. To our knowledge, this is the first report of laparoscopic management of a leaking inferior mesenteric artery caused by trauma.Case report.Successful laparoscopic management of a leaking inferior mesenteric artery secondary to trocar insertion.Laparoscopic management of a vascular injury in a hemodynamically stable patient is possible.

Abstract

To assess the accuracy of day 3 morphologic criteria in identifying the best embryos.Prospective observational study.University IVF program.One hundred cycles in women desiring blastocyst transfer who had > or =3 eight-cell embryos on day 3.On day 3, the embryologist chose the two embryos that would have been transferred that day. On day 5, embryos were examined to determine the best and second-best blastocysts.Accuracy of day 3 picks as measured in culture on day 5, outcome of nontransferred picks, and cryopreservation rate.All cycles reached the blastocyst stage and 73% had cryopreservation. The mean number of blastocysts was 4.8 (3.2 on day 5 and 1.6 on day 6). Neither pick was chosen in 39% of cycles; one pick was transferred in 38%; and both picks were transferred in 23%. Of 116 nontransferred picks, 51 were frozen and 65 arrested, with both picks arresting in 9 cycles. The single best blastocyst was chosen from the picks in 39% of cycles.Morphologic criteria for cleavage-stage embryo selection may fall short when the transfer is limited to two embryos. Culture to blastocyst is warranted in this population to avoid high-order multiples and still be able to choose the two embryos with the highest implantation potential.

Abstract

To review the authors' experience in a successful frozen blastocyst program.Retrospective study.University IVF program.Women of all ages undergoing 64 frozen blastocyst nondonor thaw cycles.Thaw cycles with day 5 or day 6 frozen blastocysts replaced into luteal day 5 endometrium in natural or programmed cycles; cryopreservation of blastocysts by Menezo two-step protocol and Testart slow cool program; thawing by two step thaw protocol.Implantation, clinical pregnancy, and delivery rates.The implantation rate was 16% and was similar with day 5 frozen blastocysts and day 6 frozen blastocysts cycles. The clinical pregnancy rate was 36% and the delivery rate was 27%, with no significant difference between day 5 and 6 blastocysts.Blastocyst cryopreservation is a viable option for patients of all ages and complements fresh blastocyst culture and transfer. The presence of good quality blastocysts for freezing on day 5 and day 6 yields comparable results and is critical for the success of thaw cycles.

Abstract

Blastocyst transfer of just one or two embryos has been used to help limit the number of high-order gestations. In this case report we describe the occurrence of a quadruplet pregnancy after the transfer of only two blastocysts during IVF. Sonographic examination showed four fetuses and what appeared to be quadriamniotic/quadrichorionic sacs, suggesting that a concomitant spontaneous conception had occurred. Definite confirmation of zygosity was obtained by genetic testing using DNA microsatellite polymorphism determinations after the birth of one boy and three girls at 32 weeks gestation. Although this event has not been reported previously, the possibility of its occurrence should be kept in mind. IVF patients with patent Fallopian tubes should be cautioned against intercourse late in their controlled ovarian stimulation, especially if they would decline multifetal reduction.

Abstract

Recombinant DNA technology makes it possible to produce large amounts of human gene products for pharmacologic applications, supplanting the need for human tissues. The genes for the alpha and beta subunits of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and human chorionic gonadotropin (hCG) have been characterized and cloned. Recombinant FSH (rFSH) has been shown to be safe and effective in the treatment of fertility disorders. In comparison with the urinary gonadotropin products, human menopausal gonadotropins (HMG), and urinary follitropins (uFSH), rFSH is more potent and better tolerated by patients. Recombinant HCG appears to be as efficacious as urinary HCG with the benefit of improved local tolerance. Recombinant LH (rLH) is likely to be recommended as a supplement to rFSH for ovulation induction in hypogonadotropic women. It may also benefit in vitro fertilization patients undergoing controlled ovarian hyperstimulation with rFSH combined with pituitary suppression, with a gonadotropin-releasing hormone agonist or antagonist.

Abstract

The aim of our study was to detect and characterize mRNA expression of VEGF isoforms VEGF(121), VEGF(145), VEGF(165), VEGF(189), and VEGF(206) in human blastocysts. We recently demonstrated VEGF mRNA expression during human preimplantation embryo development, and further information regarding the alternatively spliced mRNAs resulting in freely secreted proteins or proteins bound to cell surface heparan-sulphate proteoglycans is needed to better understand the process of angiogenesis during implantation. Human blastocysts unsuitable for transfer obtained from the IVF programme at Stanford University were examined by reverse transcription/hemi-nested polymerase chain reaction for their expression of VEGF mRNA splice variants. VEGF mRNA was expressed in 17 out of 19 (89%) blastocysts. Of the 17 blastocysts, VEGF(121) mRNA was detected in 88%, VEGF(145) mRNA in 100%, VEGF(165) mRNA in 71%, and VEGF(189) mRNA in 24% of blastocysts. There was co-expression of mRNA for VEGF(121) and VEGF(145) only in 29% blastocysts, of mRNA for VEGF(165) and VEGF(145) only in 12%, and of mRNA for VEGF(121), VEGF(145) and VEGF(165) in 59% blastocysts. VEGF(206) mRNA could not be detected. In conclusion, we demonstrated that blastocysts express the mRNAs encoding for the free VEGF proteins, enabling the implanting embryo to immediately induce angiogenesis at the implantation site.

Abstract

To detect the expression of vascular endothelial growth factor (VEGF) mRNA and/or secretion of VEGF protein by human preimplantation embryos.Human preimplantation embryos not suitable for uterine transfer were examined for beta-actin and VEGF mRNA expression. Culture media from normally fertilized and developing preimplantation embryos were assessed for VEGF protein secretion.Clinics and academic research laboratories at the Departments of Obstetrics and Gynecology at the Stanford University, Palo Alto, California and the Heinrich-Heine-University, Düsseldorf, Germany.Couples undergoing IVF by intracytoplasmic sperm injection for various reasons.Six unfertilized oocytes and 33 pathologically fertilized (tripronucleic, 3PN) preimplantation embryos were examined for VEGF mRNA expression, and 16 embryos were examined for VEGF protein secretion.Embryonic expression of VEGF mRNA and VEGF protein as determined by reverse transcription (RT)/nested polymerase chain reaction (PCR) and ELISA.VEGF mRNA and protein could not be detected in unfertilized oocytes. However, 30/33 preimplantation embryos did express VEGF mRNA (11/12 10-to-16-cell embryos, 3/4 morulae, 11/12 early blastocysts, 5/5 hatched blastocysts). The VEGF protein level was below the sensitivity of the ELISA.Production of VEGF may give the embryo the ability to induce neoangiogenesis at the implantation site, thus creating an environment necessary for its survival.

Abstract

To examine the rate of monozygotic twinning associated with blastocyst transfer using commercially available, cell-free culture systems with unmanipulated blastocysts.A retrospective analysis was conducted in multiple private and academic infertility centers throughout the United States, of 199 pregnant patients following in vitro fertilization (IVF) blastocyst embryo transfer (ET). Human embryos obtained through standard IVF stimulation protocols were cultured in commercially available, cell-free media systems and transferred as blastocysts. The main outcome measure was the rate of monozygotic twinning.A total of 199 blastocyst-ET pregnancies were achieved during the study period at the fertility centers examined. Monozygotic twinning was noted in 10/199 (5%) of these pregnancies. All were monochorionic diamnionic.Monozygotic twinning previously has been reported following IVF, especially in relation to assisted hatching. While blastocyst transfer has been available for many years using coculture, there have been no published multicenter reports of monozygotic twinning associated with unmanipulated blastocysts. In a multicenter analysis, a definite increase in monozygotic twinning was seen following blastocyst-ET. We believe this phenomenon is real and that this information should be considered when counseling patients for treatment.

Abstract

To compare implantation and pregnancy rates (PRs) achieved with blastocyst transfer (BT) and day 3 ET in similar patient populations.Retrospective analysis.Academic infertility center.One hundred consecutive patients <40 years undergoing IVF, each with more than three eight-cell embryos on day 3.Patients used their own eggs for IVF or IVF and intracytoplasmic sperm injection. Embryos were cultured in P1 medium (Irvine Scientific, Santa Ana, CA) until day 3, when they were either transferred or, in the case of embryos for BT, incubated in Blastocyst Medium (Irvine Scientific), followed by transferring on day 5.Implantation and PRs.There were no statistically significant differences in patient age, FSH level, or number of oocytes or zygotes. The BT group had fewer embryos transferred (mean, 2.4) compared with the day 3-ET group (mean, 4.6). The viable PR (cardiac activity at 6-7 weeks was considered indicative of a viable pregnancy) was higher with BT (68%, 34/50) than with day 3 ET (46%, 23/50). The implantation rate was increased with BT (47%, 56 sacs/120 embryos) compared with day 3 ET (20%, 46 sacs/231 embryos).The BT group in our study had higher implantation and PRs compared with the day 3-ET group. Better embryo selection, improved embryo-uterine synchrony, and decreased cervical mucus on day 5 may have accounted for the enhanced outcome. Our data support the use of BT to limit the number of embryos transferred while improving PRs.

Abstract

To examine the effect of the number of blastocysts transferred on pregnancy and multiple gestation rates.Retrospective study.Academic infertility center.Patients < 40 years undergoing IVF, with FSH levels of < 15 mIU/mL and more than three eight-cell embryos.Embryos were cultured in P1 until day 3 and then transferred to blastocyst medium. A maximum of three blastocysts were transferred.Pregnancy, multiple gestation, and implantation rates.All 55 patients developed blastocysts and underwent ET. Twenty-four patients had three embryos transferred and 29 patients had two embryos transferred. Two patients had only one embryo each for transfer. There was no difference in the viable pregnancy rate between the two-blastocyst transfer and three-blastocyst transfer groups (62% vs. 58%). In the two-blastocyst transfer group, 39% of pregnancies were multiple gestations (all twin gestations), compared with 79% of pregnancies in the three-blastocyst transfer group (50% twin gestations, 29% triplet gestations). The implantation rate was 47% in both groups.A commercially available, sequential culture system is highly effective for producing viable blastocysts. Two-blastocyst transfer eliminated the risk of triplets while maintaining the same high success rates seen with three-blastocyst ET.

Aspiration of a single dominant follicle leads to improved cohort development and pregnancy in a patient with poor response to in vitro fertilization treatmentFERTILITY AND STERILITYFisch, J. D., Milki, A. A.1999; 71 (6): 1147-1148

Abstract

To report improved follicular cohort development and a healthy ongoing pregnancy after midcycle aspiration of a single dominant ovarian follicle in a patient with poor response to IVF treatment.Case report.University-based infertility center.A 39-year-old woman (gravida 1, para 0) with a borderline FSH level and four previous unsuccessful IVF attempts.A single 27-mm follicular cyst was aspirated after 13 days of treatment, while controlled ovarian hyperstimulation was continued.Number of follicles developed, number of oocytes retrieved, development of a clinical pregnancy.In previous attempts, the patient had no more than two dominant follicles and a maximum of three oocytes retrieved. After midcycle aspiration of the single lead follicle, a new cohort of seven follicles developed and seven oocytes were recovered. Six embryos were replaced by tubal ET and an ongoing singleton gestation resulted.Midcycle aspiration of a single lead follicle in a patient with poor response to IVF treatment allowed the development of a larger secondary cohort of follicles during the same cycle and ultimately led to a viable pregnancy. This intervention may have future implications for the treatment of poor responders.

Sibling embryo blastocyst development correlates with the in vitro fertilization day 3 embryo transfer pregnancy rate in patients under age 40XVI World Congress on Fertility and Sterility/54th Annual Meeting of the American-Society-for-Reproductive-MedicineFisch, J. D., Milki, A. A., Behr, B.ELSEVIER SCIENCE INC.1999: 750?52

Abstract

To examine the IVF day 3-ET pregnancy rate in patients under 40 with sibling embryo blastocyst development, compared with similar patients without blastocyst formation.Retrospective analysis.Academic infertility center.One hundred twenty-five IVF day 3-ET patients under 40 with sibling embryos for extended culture.Extended culture of nontransferred sibling embryos for blastocyst development.Pregnancy and multiple gestation rates, number of oocytes, embryos formed, and embryos transferred.Thirty-eight percent of patients became pregnant. Forty-eight percent of patients had sibling embryos develop to blastocyst. The blastocyst group had more oocytes retrieved (17.4+/-6.6 versus 14.4+/-5.6), more embryos formed (11.2+/-4.2 versus 8.8+/-3.2), and a higher clinical pregnancy rate (60% versus 18%) than the group without blastocyst development.Blastocyst transfer has been shown to improve implantation rates and reduce the risk of multiple gestations from assisted reproductive technology. Sibling embryo blastocyst development may reflect superior embryo quality, as manifested by increased IVF-ET pregnancy rates. In addition to predicting pregnancy in the current cycle, sibling embryo blastocyst development may provide information about the potential for fresh blastocyst transfer in subsequent cycles and help to identify patients at risk for multiple gestations.

Abstract

This preliminary analysis was designed to quantify blastocyst development of supernumerary embryos without the use of feeder cells, conditioned medium or whole serum. Embryos derived from in-vitro fertilization (IVF) that were not transferred or cryopreserved were included in this study. Ova were harvested for IVF after a standard ovarian stimulation with gonadotrophin-releasing hormone agonist/ human menopausal gonadotrophin (GnRHa/HMG) or follicle-stimulating hormone (FSH). Ova were collected and culture in 150 microliters droplets of P1 medium under mineral oil, in groups at 37 degrees C under 5% CO2, 5% O2, 90% N2 (group A) or under 5% CO2 in air (group B) environment. Embryo transfer was performed 72 h post-harvest. Viable embryos not transferred or cryopreserved were placed in blastocyst medium and cultured for an additional 48 h in 5% CO2 in air. Embryos that exhibited an expanded blastocoelic cavity and well-defined inner cell mass at 120 h were counted. Of 838 supernumerary embryos cultured, 448 (53.5%) reached the expanded blastocyst stage by 120 h of culture. Patients were given the option of cryopreservation at that time. The embryos were cryopreserved using a standard protocol with serial addition of glycerol. Embryos reaching the blastocyst stage after more than 120 h of culture were not included. There was no difference in the proportions of blastocyst development between group A, 217/410 (53.5%) and group B, 231/428 (54%). To date, 16 patients have each had up to three thawed blastocysts transferred, out of whom seven became pregnant. This report demonstrates that a simple system of sequential culture generated acceptable, viable blastocyst development (54%) with supernumerary embryos, without the use of feeder cells, conditioned medium or whole serum. Recognizing the differential metabolic requirements of early and late cleavage stage embryos has enabled the application of a glucose/phosphate-free simple culture medium (P1) for up to 72 h of culture and a complex, glucose-containing medium (blastocyst medium) for subsequent blastocyst development.

Abstract

While torsion of the adnexa is relatively common, isolated torsion of the fallopian tube alone remains a rare occurrence. Diagnosis and surgical intervention are often delayed.A 38-year-old woman presented with acute lower right abdominal pain initially managed as renal colic. She returned to the emergency department three days later. After surgical consultation, a computed tomography scan and ultrasound showed a cystic pelvic mass with normal ovarian flow studies. Ultimately, the gynecology team performed laparoscopy with the suspicion of intermittent adnexal torsion. A 6 x 8-cm, twisted, dusky purple right fallopian tube was noted. A laparoscopic salpingectomy was performed.In the differential diagnosis of acute lower abdominal pain, isolated torsion of the fallopian tube should be considered. A timely diagnosis and surgical intervention may allow preservation of the tube. Even when irreversible damage has occurred, laparoscopic management is recommended.

Abstract

To assess the risk of probe contamination following transvaginal ultrasonography.Prospective cohort study.University Infertility Center.Women undergoing transvaginal ultrasonography.One physician obtained 840 consecutive transvaginal ultrasonograms over nine months. Latex condoms were used to cover the probe. Following examination, the condoms were removed and the probe was wiped with a germicidal disposable cloth and left to air dry for 5 minutes. Condoms were filled with water and examined for leaks.Number of perforations and distance from condom tip.Seventeen (2%) of 840 condoms leaked. The mean distance from the tip to the point of leakage was 10.6 cm +/- 2.8 (mean +/- SD; range, 7-14). Sixty-five percent of the leaks were < or = 10 cm from the tip. In several instances, two leaking condoms were found within a few examinations of each other. No visual contamination of the probe was noted.Although only 2% of condoms leaked, 65% were at distances that could have led to probe soiling intravaginally. While no body fluids were grossly visible, microscopic contamination was still possible. Since perforations were noted in close, and even consecutive scans, this study underscores the need for routine probe disinfection between examinations.

Comparison of carbon dioxide and air pneumoperitoneum for gamete intrafallopian transfer under conscious sedation and local anesthesia45th Annual Meeting of the Pacific-Coast-Fertility-SocietyMilki, A. A., Tazuke, S. I.ELSEVIER SCIENCE INC.1998: 552?54

Abstract

To compare patient tolerance and pregnancy rates (PRs) between two cohorts that underwent GIFT under local anesthesia with air versus carbon dioxide (CO2) pneumoperitoneum.Retrospective study.University clinic.Eighty-five patients who underwent 125 laparoscopies under conscious sedation for GIFT using air pneumoperitoneum were compared with 42 patients who had 70 GIFT procedures with CO2 pneumoperitoneum.Transvaginal ultrasound-guided egg retrieval followed by GIFT with compressed air or CO2 for pneumoperitoneum under local anesthesia and i.v. sedation.Patient tolerance and viable PR.The percentage of patients scoring "very good" was lower in the CO2 group (73% for air versus 57% for CO2), but the combined percentage of those scoring "very good" or "good" was comparable at 89% and 87%. The difference in the viable PRs between the two groups (43% versus 37%) for patients < 40 years old was not statistically significant.Patient tolerance and PRs are similar for air and CO2 pneumoperitoneum during GIFT under local anesthesia. Given the theoretical risk of air embolus and lack of detrimental effect of CO2 on patient tolerance and success rate, it seems prudent to use CO2 in such a setting.

Abstract

To describe our technique for laparoscopic GIFT under local anesthesia and to evaluate patient tolerance and surgeon satisfaction in 175 consecutive procedures.Prospective cohort study.University infertility practice.All GIFT candidates from 1992 to 1996 were offered the procedure. Of 119 patients, 119 chose local anesthesia for 175 procedures and 1 patient elected to have general anesthesia.Transvaginal ultrasound-guided egg retrieval followed by GIFT in the clinic procedure room with a 5-mm laparoscope and two accessory 3-mm trocars with local anesthesia and i.v. sedation.Patient tolerance and acceptance, duration of the procedure, amount of analgesics, surgeon satisfaction, and pregnancy rate (PR).The laparoscopic portion lasted an average of 27 minutes, with a mean dose of 1.41 mg of midazolam and 68 micrograms of fentanyl used. Sixty-nine percent of the patients scored "very good," 20% "good," 9% "acceptable," and 2% "poor." All 38 patients undergoing 97 repeat procedures selected local anesthesia again. For women < 40 years of age, clinical PR and delivery rate were 43% and 38%, respectively.Routine office GIFT under local anesthesia is effective and well accepted by the surgeon and is preferred by patients. It offers a significant cost containment and scheduling flexibility in addition to high success rates.

Abstract

Interleukin-1 receptor type I, IL-1 beta, IL-1 receptor antagonist, and human macrophages were immunohistochemically localized in the villous trophoblast, maternal-trophoblast interphase, and maternal decidua during early human implantation. Immunostaining for IL-1 receptor type I was present in the syncytiotrophoblast and hyperplastic endometrial glands in the maternal decidua. Immunoreactive IL-1 beta was present in the villous cytotrophoblast, syncytiotrophoblast, intermediate trophoblast, and maternal stromal decidual cells. IL-1 receptor antagonist staining was observed in the glandular endometrium of the maternal decidua and in isolated cells located inside the chorionic villi, intervillous space, and maternal decidua. Mature human macrophages, as defined by both CD/68+ and HAM56+, were present in the chorionic villi, maternal blood of intervillous space, and maternal decidua. Co-localization studies demonstrated that macrophages in all of the reported locations also stained for immunoreactive IL-1 beta. Our results show the shared presence in maternal and embryonic tissues of this receptor-agonist-antagonist system during early human implantation. This finding supports an autocrine/paracrine role for the IL-1 system in human implantation.

Abstract

Plasminogen activators and their inhibitors have been implicated in the process of fibrinolysis, tissue remodeling, and ovulation. Epidermal growth factor (EGF), a paracrine hormone found in the human ovary, increases plasminogen activator (PA) activity and the gene expression of PA and plasminogen activator inhibitor (PAI) in human endothelial cells and human cell lines. Gonadotropins also increase PA activity and gene expression in rat preovulatory granulosa cells. We have now analyzed the gene expression of PAI-1 and PAI-2 in uncultured human cumulus cells (CC), uncultured granulosa-luteal cells (GLC), and cultured GLC obtained from preovulatory follicles of patients undergoing assisted reproductive technologies. We also studied the effects of hCG and EGF on PAI-1 and PAI-2 mRNA levels in cultured GLC; GLC were cultured in serum-free medium for various times within 24 h with or without hCG and for 6 h with or without hCG, EGF, or EGF plus hCG. Total RNAs from CC and GLC were extracted, and blot hybridizations with 32P-labeled PAI-1, PAI-2, or 28S ribosomal RNA cDNA probes were performed. Both CC and GLC expressed PAI-1 and PAI-2 genes. In GLC, steady state levels of PAI-1 mRNA levels steadily increased within 24 h of culture, whereas PAI-2 levels peaked at 6 h of culture. PAI-1 mRNA levels were not affected by hCG or EGF at 6 h of culture, but PAI-2 mRNA levels were significantly increased by EGF at 6 h of culture. These studies demonstrate that human GLC PAI-1 and PAI-2 mRNA levels are differentially regulated and suggest that EGF may be involved in modulation of the human ovarian PA system during the periovulatory period.

Abstract

To improve the assessment of sperm penetration during the hamster penetration assay, we compared the Hoechst 33342 and 33258 DNA-specific fluorescent stains with the standard acetolacmoid stain. The fluorescence stains produced distinct staining of the DNA within the egg cytoplasm and nucleus, and this allowed for accurate and fast assessment of sperm penetration.

Abstract

Local anesthesia with conscious sedation is well accepted by patients and provides scheduling flexibility, cost containment, patient safety, and ease of recovery. We believe the technique should be offered to selected patients undergoing intrafallopian transfer. By adhering to specific guidelines for surgical technique and monitoring, the procedure is a safe and acceptable alternative to general anesthesia for laparoscopic intrafallopian transfers.

Abstract

Fine open-end ET catheters offer several benefits and are now commonly used in IVF-ET procedures. However, they are not always easy to thread into the uterine cavity. We describe a metallic cervical cannula that allows the use of the popular Tomcat catheter in the majority of patients in whom we were unable to achieve a successful ET with the Tomcat alone.

Abstract

To determine if luteinizing human granulosa cells contain messenger ribonucleic acid (mRNAs) encoding insulin-like growth factor-binding protein (IGFBPs) and if cultured granulosa secrete IGFBPs into conditioned medium (CM).Northern analysis, using IGFBP-specific complementary deoxyribonucleic acid probes, was used to detect granulosa-derived IGFBP mRNAs. Western ligand blot analysis of CM was used to detect IGFBPs secreted by granulosa cultures with and without human chorionic gonadotropin (hCG).Granulosa cells were obtained from the In Vitro Fertilization (IVF) Program at Stanford University, a private teaching institution.Patients undergoing IVF for tubal disease.None.Transcripts of IGFBP mRNA and IGFBPs secreted into CM were detected by autoradiography of Northern and Western ligand blots, respectively.Transcripts of IGFBP-3, IGFBP-2, and IGFBP-1 mRNA were detected in human luteinizing granulosa. Cultured granulosa secreted IGFBPs with molecular weights corresponding to IGFBP-3, IGFBP-2, and IGFBP-1, and the latter two IGFBPs increased with 10 ng/mL hCG. A 24 kd IGFBP was noted, which may be newly characterized IGFBP-4.These data show that luteinizing human granulosa cells express mRNAs encoding three IGFBPs, secrete IGFBPs into culture medium, and that production of at least two of the IGFBPs is hCG-dependent, further supporting a role for the IGF system in human folliculogenesis.